Shuhei Mayanagi1, Minoru Kitago1, Toshiharu Sakurai2, Tatsuo Matsuda1, Tomonobu Fujita2, Hajime Higuchi3, Junichi Taguchi4, Hiroya Takeuchi1, Osamu Itano1, Koichi Aiura5, Yasuo Hamamoto6, Hiromasa Takaishi6, Masato Okamoto7,2, Makoto Sunamura8, Yutaka Kawakami2, Yuko Kitagawa1
1Department of Surgery, Keio University School of Medicine, Tokyo, Japan
2Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
3Department of Internal Medicine Clinical Oncology Center Kitasato University Kitasato Institute Hospital Tokyo Japan
4Tokyo Midtown Clinic, Tokyo, Japan
5Department of Surgery, Kawasaki Municipal Hospital, Kawasaki, Japan
6Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
7Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo, Japan
8Department of Digestive Tract Surgery and Transplantation Surgery Hachioji Medical Center Tokyo Medical University Tokyo Japan
Tóm tắt
This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (WT1) peptide‐pulsed dendritic cell vaccination combined with gemcitabine (DCGEM) as a first‐line therapy among patients with advanced pancreatic cancer. Ten HLA‐A*2402 patients were treated with WT1 peptide‐pulsed DC vaccination (1 × 107 cells) on days 8 and 22 and gemcitabine (1000 mg/m2) on days 1, 8 and 15. Induction of a WT1‐specific immune response was evaluated using the delayed‐type hypersensitivity (DTH) skin test, interferon‐γ enzyme‐linked immunospot and HLA tetramer assays, along with assays for various immunological factors. DCGEM was well‐tolerated, and the relative dose intensity of gemcitabine was 87%. Disease control associated with a low neutrophil/lymphocyte ratio was observed in all three patients with DTH positivity; it was also correlated with a low percentage of granulocytic myeloid derived suppressor cells in the pretreatment peripheral blood (P = 0.017). Patients with liver metastases and high levels of inflammatory markers such as C‐reactive protein and interleukin‐8 (IL‐8) showed poor survival even though a WT1‐specific immune response was induced in them. WT1 peptide‐pulsed DCGEM is feasible and effective for inducing anti‐tumor T‐cell responses. Our results support future investigations for pancreatic cancer patients with non‐liver metastases and favorable immunological conditions. This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (http://www.umin.ac.jp/ctr/ number: UMIN‐000004855).
